The ability to adapt to a low protein intake is essential to the survival and well being of patients with reduced renal function. The adaptation occurs in the presence of many compounds not retained by normal people, some of which are peculiar to the renal patient. The guanidines are a class of compounds of particular interest both in N metabolism and to the uremic; guanidinosuccinate and gamma-guanidinopropionate, not readily detected in normal man, are formed and appear in blood and urine of renal patients. The metabolic relationship of these unique compounds to arginine, creatine and its precursor, guanidinoacetate, is not known. Published reports have failed to demonstrate a correlation between their concentrations and symptoms of uremia. However, the presence of these compounds indicate an altered and adapted metabolism. The concept that the presence of these compounds indicates a favorable adaptation has not been explored. The proposed studies will investigate the occurrence of the guanidines and their metabolic origin to test this concept. Thus, special emphasis will be placed on the relationship of tissue concentrations of these compounds and their precursors, the presence and activities of enzymes in selected tissues and occurrence of metabolites in blood and urine in experimentally uremic animals and uremic man. The results of this investigation will further our understanding of the adaptive process in patients with renal disease in order to increase the available biochemical techniques through which the state of the uremic patient can be monitored.